Department of Ophthalmology and Visual Sciences, Nagoya City University Graduate School of Medicine, Aichi 467-8601, JapanDepartment of Ophthalmology and Eye Clinic, University of Leipzig, Faculty of Medicine, Leipzig D-04103, Germany

Department of Ophthalmology and Visual Sciences, Nagoya City University Graduate School of Medicine, Aichi 467-8601, JapanDepartment of Ophthalmology and Eye Clinic, University of Leipzig, Faculty of Medicine, Leipzig D-04103, Germany

ABSTRACT

Age-related macular degeneration (AMD) is a leading cause of blindness in people over 50 years of age in many developed countries. Drusen are yellowish extracellular deposits beneath retinal pigment epithelium (RPE) found in aging eyes and considered as a biomarker of AMD. However, the biogenesis of drusen has not been elucidated. We reported previously that multicellular spheroids of human RPE cells constructed a well-differentiated monolayer of RPE with a Bruch's membrane. We determined that RPE spheroids exhibited drusen formation between the RPE and Bruch's membrane with expression of many drusen-associated proteins, such as amyloid β and complement components, the expression of which was altered by a challenge with oxidative stress. Artificial lipofuscin-loaded RPE spheroids yielded drusen more frequently. In the current study, we showed that drusen originates from the RPE. This culture system is an attractive tool for use as an in vitro drusen model, which might help elucidate the biogenesis of drusen and the pathogenesis of related diseases, such as AMD.

This investigation was supported by the Deutsche Forschungsgemeinschaft (grant WI880/9-1), and by a 2016 Japan Society for the Promotion of Science Grant-in-Aid for Scientific Research (no. 16K11293) to T.Y.

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